Chapter 14- Mesoderm-paraxial and intermediate

Recall lineages

Fig. 12.4

Fig. 14.1- mesoderm lineages

Fig. 14.2- mesoderm lineages in chick

24hr

48hr

Intermediate

Kidney, gonads

Paraxial

Head Somite

Cartilage,skeletal, dermis

Lateral

Circulatory,Body cavity,

extraembryonic

Notochord

Chapter 14- Mesoderm-paraxial and intermediate

Paraxial

Head Somite

Cartilage,skeletal, dermis

4 components of somite formation

1. Periodicity-

• total number of somites is 50 in chicks, 65 in mice

• somites form from cell groupings in regular intervals

Paraxial mesoderm

Fig. 14.3

Neural tube

Mechanism? Involves the hairy geneHairy gene expression correlates with positioning of somites

•This effect is independent of all surrounding tissue

2. Epithelialization- mesenchyme is converted to epithelium prior to final somite formation

• EM proteins fibronectin and N-cadherin link cells into clustered units

Paraxial

Head Somite

Cartilage,skeletal, dermis

4 components of somite formation (cont.)

3. Axial specification

•Distinct somites give rise to distinct structures

Paraxial mesoderm

Fig. 11.40-Mouse somites mapped to vertebrate regions and to specific hox gene expression

4. Differentiation- somites form 1) cartilage of vertabrae and ribs, 2) muscles of rib cage, limbs and back, and 3) dermis of the dorsal skin

•Specific hox gene expression predicts the type of vertebra formed

hox5

Somites

hox6 hox9 hox10

Paraxial

Head Somite

Cartilage,skeletal, dermis

4 components of somite formation (cont.)

Paraxial mesoderm

4. Differentiation (cont)- somites form: 1) cartilage of vertabrae and ribs

2) muscles of rib cage, limbs and back3) dermis of the dorsal skin

Some somite cells become mesenchymal cells again to form sclerotome- these will become cartilage of vertebrae and ribs

Fig. 14.7

Paraxial

Head Somite

Cartilage,skeletal, dermis

4 components of somite formation

Paraxial mesoderm

4. Differentiation- (continued)

Fig. 14.9

Somite has three additional regions that follow distinct fates

1. Dermis

3. Body wall Muscles

2. Back muscles

Sclerotome

Neural tube produces NT-3 and Wnt proteins that influence somite cell fate

Notochord produces sonic hedgehog to influence sclerotome fate

A

A

B

B

MyogenesisWhat dictates the muscle phenotype?

Pax3 is a transcription factor that activates transcription factors Myf5 and MyoD

Pax3Wnt? + MyoDMyf5

MyoD binding site Muscle-specific genes

Signaling pathway to activate muscle-specific genes (Fig. not in text)

Introduction of MyoD into other cell types converts them to muscle

Myoblasts fuse to form myotubes to produce muscle fibers

Fig. 14.10

Osteogenesis (Bone development)What dictates the bone development?

There are three lineages that produce bone-1) Somites (vertebrae/ribs)2) Lateral mesoderm (limbs)- Not yet discussed3) Cranial Neural crest (head/face)

Osteogenesis occurs by two mechanisms1) Intramembrane ossification- bone withour cartilage precursor2) Endochondral ossification- cartilage converted to bone

Neural crest cells Mesenchyme Cell clustering

Differentiate into osteoblast (secrete

collogen-proteoglycan matrix)

Differentiate into osteocyte (bone cell)

1. Intramembrane ossification

Mechanism of intramembranous ossification)

Transcription factor CBFA1 plays a key role

BMP proteins also are important

Mesenchyme Differentiate into osteoblast

CBFA1

Activates expression of several bone-specific genes

CFBA1 KO- all ossification prevented

Fig. 14.12

Blue- cartilageRed- Bone

WT CFB1A -/-

Human disease- cleidocranial dysplasia (CCD)- due to mutaions in the CBFA1 gene

1. Intramembrane ossification (cont.)

Mesenchyme cartilage

Proliferate and form model of bone by producing an EM

Pax

2. Endochondral ossification

Differentiate into chondrocytes

Blood vessels invade,

Chondocytes die

Proliferation ceases, matrix

is modified

Adjacent cells (not

chondrocytes) differentiate into osteoblasts to fill

in boneA

A B

B

E D

C

C D E

Fig. 14.13

Osteoclasts are cells which hollow out bones to form cavities

• Osteoclasts enter through blood vessels• Osteoclasts are likely form blood-lineage precursors

The disease ostroporosis occurs if too much osteoclast activity- bones become brittle

The disease ostropetrosis occurs if too little osteoclast activity- bones are not hollowed out enough

Intermediate Mesoderm

Recall lineages

Fig. 12.4

Fig. 14.1- mesoderm lineages

Intermediate Paraxial Lateral

HeadKidney, gonads

Somite

Cartilage,skeletal, dermis

Circulatory,Body cavity,

extraembryonic

Kidney development

Three stages1. Pronephric duct arises from intermediate mesoderm just ventral to anterior somites and migrate toward head

Kidney development

Three stages

1. Pronephric duct arises from intermediate mesoderm just ventral to anterior somites and migrates toward tail 2. Migrating nephric duct cells induce mesenchyme to form pronephros (tubules)

3. Pronephric tubules degenerate, but a new set of mesonephros tubules are formed (approx 30 in humans) further down

The mesonephros produces hematopoietic stem cells and, in some mammals, become sperm carrying tubes

Pronephros

The metanephros tubules are formed from mesenchyme, which induces ureteric buds (these become ureters that transport urine from bladder)

Nephric Duct

Fig. 14.18

Fig. 14.19

Ureteric bud and metanephrogenic mesenchyme interact to become the kidney- called reciprocal induction

Mechanism of reciprocal induction1. Metanephrogenic mesenchyme formed

2. Metanephrogenic mesenchyme secretes GDNF and HGF to induce ureteric bud form

3. Ureteric bud secretes FGF2 and BMP2 to prevent apoptosis of Metanephrogenic mesenchyme

4. ureteric bud secretes LIF to induce mesenchyme cells to aggregate and become epithelial

5. Metanephrogenic mesenchyme induces branching of ureteric bud

6. Differentiation and growth of the ureteric bud.